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TitleStructure and mechanism of NALCN-FAM155A-UNC79-UNC80 channel complex.
Journal, issue, pagesNat Commun, Vol. 13, Issue 1, Page 2639, Year 2022
Publish dateMay 12, 2022
AuthorsYunlu Kang / Lei Chen /
PubMed AbstractNALCN channel mediates sodium leak currents and is important for maintaining proper resting membrane potential. NALCN and FAM155A form the core complex of the channel, the activity of which ...NALCN channel mediates sodium leak currents and is important for maintaining proper resting membrane potential. NALCN and FAM155A form the core complex of the channel, the activity of which essentially depends on the presence of both UNC79 and UNC80, two auxiliary proteins. NALCN, FAM155A, UNC79, and UNC80 co-assemble into a large hetero-tetrameric channel complex. Genetic mutations of NALCN channel components lead to neurodevelopmental diseases. However, the structure and mechanism of the intact channel complex remain elusive. Here, we present the cryo-EM structure of the mammalian NALCN-FAM155A-UNC79-UNC80 quaternary complex. The structure shows that UNC79-UNC80 form a large piler-shaped heterodimer which was tethered to the intracellular side of the NALCN channel through tripartite interactions with the cytoplasmic loops of NALCN. Two interactions are essential for proper cell surface localization of NALCN. The other interaction relieves the self-inhibition of NALCN by pulling the auto-inhibitory CTD Interacting Helix (CIH) out of its binding site. Our work defines the structural mechanism of NALCN modulation by UNC79 and UNC80.
External linksNat Commun / PubMed:35550517 / PubMed Central
MethodsEM (single particle)
Resolution3.2 Å
Structure data

32344

7w7g

EMDB-32344, PDB-7w7g:
Structure of Mammalian NALCN-FAM155A-UNC79-UNC80 quanternary complex
Method: EM (single particle) / Resolution: 3.2 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • mus musculus (house mouse)
  • rattus norvegicus (Norway rat)
KeywordsMEMBRANE PROTEIN / Sodium leak channel / NALCN / channel / FAM155 / UNC79 / UNC80

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